The present invention relates generally to a method for analyzing analytes in a biological sample, and more specifically to determining a relative proportion (also called a ratio herein) of concentrations of analytes in a biological sample.
Computing the ratio of two or more analytes in a sample is a useful comparison in a variety of contexts. Ratios are frequently used to compensate for variability in the composition or concentration of the analytes in a sample. For example, when measuring analytes present in urine, the concentration of analytes in any given sample can vary significantly. These concentration fluctuations can be normalized by creating a ratio between different analytes present in a sample. For example, a ratio can be created between the concentration of a urinary analyte and the concentration of creatinine in urine. Creating this relationship between two analytes in the sample allows for a more meaningful measurement in light of the concentration fluctuations. It is also possible to normalize the concentration of a desired analyte in tissue against the concentration of total protein or a specific protein such as, for example, albumin. Ratios can also compensate for correlated errors in the measurement, e.g., dilution errors.
One context for computing a ratio is the determination of percent hemoglobin A1c (HbA1c). HbA1c is the amount of glycated hemoglobin in a blood sample. The percent HbA1c can be obtained from a proportion of the concentration of HbA1c to the concentration of total hemoglobin. Percent HbA1c is useful in determining a response to therapy in diabetics, and also for diagnosing diabetics.
Reference methods to determine the ratio are not practical for general diagnosis, due to cost and speed. Common methods for determining a ratio between two analytes (e.g. for diagnosis) are often complicated to determine and/or inaccurate. For example, dividing one concentration by the other concentration provides inaccurate results, e.g., as interactions between analytes are ignored. For instance, in some measurement techniques, such as immunoassay, the first antibody used to measure the first analyte response may also interact with the second analyte in the sample.
Therefore, it is desirable for new methods, systems, and apparatus for determining a proportion of two analytes to each other in an efficient and accurate manner.